Human tuberculosis caused by Mycobacterium tuberculosis is a severe global health problem responsible for approximately 3 million deaths annually (NIH report). The worldwide incidence of new tuberculosis cases has been progressively falling for the last decade but the recent years has markedly changed this trend due to the advent of AIDS and the appearance of multidrug resistant strains of M. tuberculosis (Rieder).
The only vaccine presently available is BCG, a vaccine which efficacy remains a matter of controversy. BCG generally induces a high level of acquired resistance in animal models of tuberculosis (Smith), but several human trials in developing countries have failed to demonstrate significant protection (Fine).
This makes the development of a new and improved vaccine against tuberculosis an urgent matter which has been given a very high priority by the WHO (WHO BULL). Many attempts to define protective mycobacterial substances have been made, and from 1950 to 1970 several investigators reported an increased resistance after experimental vaccination. However, the demonstration of a specific long-term protective immune response with the potency of BCG has not yet been achieved by administration of soluble proteins or cell wall fragments. Immunity to M. tuberculosis is characterized by three basic features; i) Living bacilli efficiently induces a protective immune response in contrast to killed preparations (Orme); ii) Specifically sensitized T lymphocytes mediate this protection (Mackaness, Orme); iii) The most important mediator molecule seems to be interferon gamma (INF-.gamma.) (Rook, Flesh).
Proteins secreted by M. tuberculosis when grown in culture have been demonstrated to function as stimulators of specific cellular immune responses in mice, and it has been suggested that possible antigens useful in new vaccines against tuberculosis should be sought among such proteins. However, no immune dominant antigen has been isolated or identified.